Bilateral Shifts in Deuterium Supply Similarly Change Physiology of the Pituitary-Thyroid Axis, but Differentially Influence Na+/I- Symporter Production.

Deuterium, a stable isotope of hydrogen, is abundant in organisms. It is known to produce various biological effects. However, its impact in thyroid hormone synthesis and secretion is poorly studied. The aim of this investigation was to evaluate the dynamics of thyroid hormones and pituitary thyroid-stimulating hormone secretion during bilateral shifts in deuterium supply and assess a possible role of the Na+/I- symporter (NIS), the main iodide transporter, in altered thyroid function. The experiment was performed on adult male Wistar rats, which consumed deuterium-depleted ([D] = 10 ppm) and deuterium-enriched ([D] = 500,000 ppm) water for 21 days. The assessment of total thyroxine and triiodothyronine and their free fractions, as well as thyroid-stimulating hormone in blood serum, revealed the rapid response of the thyroid gland to shifts in the deuterium/protium balance. The present investigation shows that the bilateral changes in the deuterium body content similarly modulate thyroid hormone production and functional activity of the pituitary gland, but the responses of the thyroid and pituitary glands differ. The response of the thyroid cells was to increase the synthesis of the hormones and the pituitary thyrotropes, in order to reduce the production of the thyroid-stimulating hormone. The evaluation of NIS serum levels found a gradual increase in the rats that consumed deuterium-enriched water and no differences in the group exposed to deuterium depletion. NIS levels in both groups did not correlate with thyroid hormones and pituitary thyroid-stimulating hormone production. The data obtained show that thyroid gland has a higher sensitivity to shifts in the deuterium body content than the hypothalamic-pituitary complex, which responded later but similarly in the case of deuteration or deuterium depletion. It indicates a different sensitivity of the endocrine glands to alterations in deuterium content. It suggests that thyroid hormone production rate may depend on deuterium blood/tissue and cytosol/organelle gradients, which possibly disturb the secretory process independently of the NIS.

Emerging Role of Deuterium/Protium Disbalance in Cell Cycle and Apoptosis.

Deuterium, a stable isotope of hydrogen, is a component of water and organic compounds. It is the second most abundant element in the human body after sodium. Although the concentration of deuterium in an organism is much lower than that of protium, a wide variety of morphological, biochemical, and physiological changes are known to occur in deuterium-treated cells, including changes in fundamental processes such as cell division or energy metabolism. The mode and degree of changes in cells and tissues, both with an increase and a decrease in the concentration of deuterium, depends primarily on the time of exposure, as well as on the concentration. The reviewed data show that plant and animal cells are sensitive to deuterium content. Any shifts in the D/H balance outside or inside cells promote immediate responses. The review summarizes reported data on the proliferation and apoptosis of normal and neoplastic cells in different modes of deuteration and deuterium depletion in vivo and in vitro. The authors propose their own concept of the effects of changes in deuterium content in the body on cell proliferation and death. The altered rate of proliferation and apoptosis indicate a pivotal role of the hydrogen isotope content in living organisms and suggest the presence of a D/H sensor, which is yet to be detected.

Deuterium Content of the Organic Compounds in Food Has an Impact on Tumor Growth in Mice.

Research with deuterium-depleted water (DDW) in the last two decades proved that the deuterium/hydrogen ratio has a key role in cell cycle regulation and cellular metabolism. The present study aimed to investigate the possible effect of deuterium-depleted yolk (DDyolk) alone and in combination with DDW on cancer growth in two in vivo mouse models. To produce DDyolk, the drinking water of laying hens was replaced with DDW (25 ppm) for 6 weeks, resulting in a 60 ppm D level in dried egg yolk that was used as a deuterium-depleted food additive. In one model, 4T1, a cell line with a high metastatic capacity to the lung was inoculated in the mice's mammary pad. After three weeks of treatment with DDW and/or DDyolk, the tumor volume in the lungs was smaller in all treated groups vs. controls with natural D levels. Tumor growth and survival in mice transplanted with an MCF-7 breast cancer cell line showed that the anticancer effect of DDW was enhanced by food containing the deuterium-depleted yolk. The study confirmed the importance of the D/H ratio in consumed water and in metabolic water produced by the mitochondria while oxidizing nutrient molecules. This is in line with the concept that the initiation of cell growth requires the cells to generate a higher D/H ratio, but DDW, DDyolk, or the naturally low-D lipids in a ketogenic diet, have a significant effect on tumor growth by preventing the cells from raising the D/H ratio to the threshold.

Blocking the Increase of Intracellular Deuterium Concentration Prevents the Expression of Cancer-Related Genes, Tumor Development, and Tumor Recurrence in Cancer Patients.

The possible role of the naturally occurring deuterium in the regulation of cell division was first described in the 1990s. To investigate the mechanism of influence of deuterium (D) on cell growth, expression of 236 cancer-related and 536 kinase genes were tested in deuterium-depleted (40 and 80 ppm) and deuterium-enriched (300 ppm) media compared to natural D level (150 ppm). Among genes with expression changes exceeding 30% and copy numbers over 30 (124 and 135 genes, respectively) 97.3% of them was upregulated at 300 ppm D-concentration. In mice exposed to chemical carcinogen, one-year survival data showed that deuterium-depleted water (DDW) with 30 ppm D as drinking water prevented tumor development. One quarter of the treated male mice survived 344 days, the females 334 days, while one quarter of the control mice survived only 188 and 156 days, respectively. In our human retrospective study 204 previously treated cancer patients with disease in remission, who consumed DDW, were followed. Cumulative follow-up time was 1024 years, and average follow-up time per patient, 5 years (median: 3.6 years). One hundred and fifty-six patients out of 204 (77.9%) did not relapse during their 803 years cumulative follow-up time. Median survival time (MST) was not calculable due to the extremely low death rate (11 cancer-related deaths, 5.4% of the study population). Importantly, 8 out of 11 deaths occurred several years after stopping DDW consumption, confirming that regular consumption of DDW can prevent recurrence of cancer. These findings point to the likely mechanism in which consumption of DDW keeps D-concentration below natural levels, preventing the D/H ratio from increasing to the threshold required for cell division. This in turn can serve as a key to reduce the relapse rate of cancer patients and/or to reduce cancer incidence in healthy populations.

Reactive Alterations in Thymic Lymphocytopoiesis to Short-Term Decrease in Deuterium Content in the Body.

We studied changes in thymic lymphocytopoiesis induced by a short-term decrease in deuterium content in the body. The experiment was performed on adult male Wistar rats receiving water with lower deuterium content [D]=10 ppm. Increased relative weight of thymus was found after 24 h of consumption. Flow cytometry revealed higher percentage of undifferentiated cells and mature T cells, especially cytotoxic T cells. Hence, lymphocytopoiesis in the thymus is highly sensitive to short-term decrease in deuterium body content. A decrease in the content of deuterium stimulates proliferation of lymphoblasts in the thymus and slows down migration of differentiated T cells. Enhanced generation of cytotoxic T cells under these conditions attests to the role of deuterium in selection of double-positive thymocytes. The revealed shifts are reactive, and their pattern can change later, which requires further research.

Deuterium-depleted water stimulates GLUT4 translocation in the presence of insulin, which leads to decreased blood glucose concentration.

Deuterium (D) is a stable isotope of hydrogen (H) with a mass number of 2. It is present in natural waters in the form of HDO, at a concentration of 16.8 mmol/L, equivalent to 150 ppm. In a phase II clinical study, deuterium depletion reduced fasting glucose concentration and insulin resistance. In this study, we tested the effect of subnormal D-concentration on glucose metabolism in a streptozotocin (STZ)-induced diabetic rat model. Animals were randomly distributed into nine groups to test the effect of D2O (in a range of 25-150 ppm) on glucose metabolism in diabetic animals with or without insulin treatment. Serum glucose, fructose amine-, HbA1c, insulin and urine glucose levels were monitored, respectively. After the 8-week treatment, membrane-associated GLUT4 fractions from the soleus muscle were estimated by Western blot technique. Our results indicate that, in the presence of insulin, deuterium depletion markedly reduced serum levels of glucose, -fructose amine, and -HbA1c, in a dose-dependent manner. The optimal concentration of deuterium was between 125 and 140 ppm. After a 4-week period of deuterium depletion, the highest membrane-associated GLUT4 content was detected at 125 ppm. These data suggest that deuterium depletion dose-dependently enhances the effect of insulin on GLUT4 translocation and potentiates glucose uptake in diabetic rats, which explains the lower serum glucose, -fructose amine, and -HbA1c concentrations. Based on our experimental data, deuterium-depleted water could be used to treat patients with metabolic syndrome (MS) by increasing insulin sensitivity. These experiments indicate that naturally occurring deuterium has an impact on metabolic regulations.

Deuterium Depletion Inhibits Cell Proliferation, RNA and Nuclear Membrane Turnover to Enhance Survival in Pancreatic Cancer.

The effects of deuterium-depleted water (DDW) containing deuterium (D) at a concentration of 25 parts per million (ppm), 50 ppm, 105 ppm and the control at 150 ppm were monitored in MIA-PaCa-2 pancreatic cancer cells by the real-time cell impedance detection xCELLigence method. The data revealed that lower deuterium concentrations corresponded to lower MiA PaCa-2 growth rate. Nuclear membrane turnover and nucleic acid synthesis rate at different D-concentrations were determined by targeted [1,2-13C2]-D-glucose fate associations. The data showed severely decreased oxidative pentose cycling, RNA ribose 13C labeling from [1,2-13C2]-D-glucose and nuclear membrane lignoceric (C24:0) acid turnover. Here, we treated advanced pancreatic cancer patients with DDW as an extra-mitochondrial deuterium-depleting strategy and evaluated overall patient survival. Eighty-six (36 male and 50 female) pancreatic adenocarcinoma patients were treated with conventional chemotherapy and natural water (control, 30 patients) or 85 ppm DDW (56 patients), which was gradually decreased to preparations with 65 ppm and 45 ppm deuterium content for each 1 to 3 months treatment period. Patient survival curves were calculated by the Kaplan-Meier method and Pearson correlation was taken between medial survival time (MST) and DDW treatment in pancreatic cancer patients. The MST for patients consuming DDW treatment (n = 56) was 19.6 months in comparison with the 6.36 months' MST achieved with chemotherapy alone (n = 30). There was a strong, statistically significant Pearson correlation (r = 0.504, p < 0.001) between survival time and length and frequency of DDW treatment.

Anticancer Effect of Deuterium Depleted Water - Redox Disbalance Leads to Oxidative Stress.

Despite the convincing empirical evidence that deuterium depleted water (DDW, 25-125 ppm deuterium) has anticancer effect, the molecular mechanism remains unclear. Here, redox proteomics investigation of the DDW action in A549 cells revealed an increased level of oxidative stress, whereas expression proteomics in combination with thermal profiling uncovered crucial role of mitochondrial proteins. In the proposed scenario, reversal of the normally positive deuterium gradient across the inner membrane leads to an increased export of protons from the matrix to intermembrane space and an increase in the mitochondrial membrane potential, enhancing the production of reactive oxygen species (ROS). The resulting oxidative stress leads to slower growth and can induce apoptosis. However, further deuterium depletion in ambient water triggers a feedback mechanism, which leads to restoration of the redox equilibrium and resumed growth. The DDW-induced oxidative stress, verified by traditional biochemical assays, may be helpful as an adjuvant to ROS-inducing anticancer therapy.

Electrophysiological Activity and Survival Rate of Rats Nervous Tissue Cells Depends on D/H Isotopic Composition of Medium.

The deuterium content modification in an organism has a neuroprotective effect during the hypoxia model, affecting anxiety, memory and stress resistance. The aim of this work was to elucidate the possible mechanisms of the medium D/H composition modification on nerve cells. We studied the effect of an incubation medium with a 50 ppm deuterium content compared to a medium with 150 ppm on: (1) the activity of Wistar rats' hippocampus CA1 field neurons, (2) the level of cultured cerebellar neuron death during glucose deprivation and temperature stress, (3) mitochondrial membrane potential (MMP) and the generation of reactive oxygen species in cultures of cerebellar neurons. The results of the analysis showed that the incubation of hippocampal sections in a medium with a 50 ppm deuterium reduced the amplitude of the pop-spike. The restoration of neuron activity was observed when sections were returned to the incubation medium with a 150 ppm deuterium content. An environment with a 50 ppm deuterium did not significantly affect the level of reactive oxygen species in neuron cultures, while MMP decreased by 16-20%. In experiments with glucose deprivation and temperature stress, the medium with 50 ppm increased the death of neurons. Thus, a short exposure of nerve cells in the medium with 50 ppm deuterium acts as an additional stressful factor, which is possibly associated with the violation of the cell energy balance. The decrease in the mitochondrial membrane potential, which is known to be associated with ATP synthesis, indicates that this effect may be associated with the cell energy imbalance. The decrease in the activity of the CA1 field hippocampal neurons may reflect reversible adaptive changes in the operation of fast-reacting ion channels.

Reduction of Deuterium Level Supports Resistance of Neurons to Glucose Deprivation and Hypoxia: Study in Cultures of Neurons and on Animals.

The effect of a reduced deuterium (D) content in the incubation medium on the survival of cultured neurons in vitro and under glucose deprivation was studied. In addition, we studied the effect of a decrease in the deuterium content in the rat brain on oxidative processes in the nervous tissue, its antioxidant protection, and training of rats in the T-shaped maze test under hypoxic conditions. For experiments with cultures of neurons, 7-8-day cultures of cerebellar neurons were used. Determination of the rate of neuronal death in cultures was carried out using propidium iodide. Acute hypoxia with hypercapnia was simulated in rats by placing them in sealed vessels with a capacity of 1 L. The effect on oxidative processes in brain tissues was assessed by changes in the level of free radical oxidation and malondialdehyde. The effect on the antioxidant system of the brain was assessed by the activity of catalase. The study in the T-maze was carried out in accordance with the generally accepted methodology, the skill of alternating right-sided and left-sided loops on positive reinforcement was developed. This work has shown that a decrease in the deuterium content in the incubation medium to a level of -357‱ has a neuroprotective effect, increasing the survival rate of cultured neurons under glucose deprivation. When exposed to hypoxia, a preliminary decrease in the deuterium content in the rat brain to -261‱ prevents the development of oxidative stress in their nervous tissue and preserves the learning ability of animals in the T-shaped maze test at the level of the control group. A similar protective effect during the modification of the 2H/1H internal environment of the body by the consumption of DDW can potentially be used for the prevention of pathological conditions associated with the development of oxidative stress with damage to the central nervous system.

Neuroprotective Effects of Deuterium-Depleted Water (DDW) Against H2O2-Induced Oxidative Stress in Differentiated PC12 Cells Through the PI3K/Akt Signaling Pathway.

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Induction of endogenous antioxidants to act against oxidative stress-mediated neuronal damage seems to be a reasonable strategy for delaying the progression of such diseases. In this study, we investigated the neuroprotective effect of deuterium-depleted water (DDW) against H2O2-induced oxidative stress in differentiated PC12 cells and the possible signaling pathways involved. The differentiated PC12 cell line was pretreated with DDW containing different concentrations (50-100 ppm) of deuterium and then treated with H2O2 to induce oxidative stress and neurotoxicity. We assessed cell survival, reactive oxygen species (ROS) generation, TUNEL assay, catalase (CAT), copper and zinc-containing superoxide dismutase (CuZn-SOD) and superoxide dismutase (SOD) activity and performed Western blot analysis to investigate the neuroprotective effect of DDW. The results indicated that DDW could attenuate H2O2-induced apoptosis, reduce ROS formation, and increase CAT, CuZn-SOD and SOD activity in H2O2-treated PC12 cells. Western blot analysis revealed that DDW treatment significantly increased the expression of p-Akt, Bcl-2 and GSK-3ß. However, the protective effect of DDW on cell survival and the DDW-mediated increases in p-Akt, Bcl-2 and GSK-3ß were abolished by pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002. In summary, DDW may protect differentiated PC12 cells against H2O2-induced oxidative stress through the PI3K/Akt signaling pathway.

Dependence of Biocatalysis on D/H Ratio: Possible Fundamental Differences for High-Level Biological Taxons.

The kinetics of biological reactions depends on the deuterium/protium (D/H) ratio in water. In this work, we describe the kinetic model of biocatalytic reactions in living organisms depending on the D/H ratio. We show that a change in the lifetime or other characteristics of the vital activity of some organisms in response to a decrease or increase in the content of deuterium in the environment can be a sign of a difference in taxons. For animals-this is a curve with saturation according to the Gauss's principle, for plants-it is the Poisson dependence, for bacteria a weakly saturated curve with a slight reaction to the deuterium/protium ratio toward increasing deuterium. The biological activity of the aquatic environment with reduced, elevated, and natural concentrations of deuterium is considered. The results of the study are presented in different vital indicators of some taxons: the bacteria kingdom-the colony forming units (CFU) index (Escherichia coli); animals-the activation energy of the death of ciliates (Spirostomum ambiguum), embryogenesis of fish (Brachydanio rerio); plants-germination and accumulation of trace elements Callisia fragrans L., sprouting of gametophores and peptidomics of moss Physcomitrella patens. It was found that many organisms change their metabolism and activity, responding to both high and low concentrations of deuterium in water.

Effect of Systemic Subnormal Deuterium Level on Metabolic Syndrome Related and other Blood Parameters in Humans: A Preliminary Study.

The effects of deuterium depletion on the human organism have been, except for the antitumor action, seldom investigated by now and the available data are scarce. In oncological patients who also suffered from diabetes and were treated with deuterium-depleted water (DDW), an improvement of glucose metabolism was observed, and rat studies also proved the efficacy of DDW to reduce blood sugar level. In the present work, 30 volunteers with pre- or manifest diabetes were enrolled to a clinical study. The patients received 1.5 L of water with reduced deuterium content (104 ppm instead of 145 ppm, equivalent 12 mmol/L in human) daily for 90 days. The effects on fasting glucose and insulin level, on peripheral glucose disposal, and other metabolic parameters were investigated. Fasting insulin and glucose decreased, and insulin reaction on glucose load improved, in 15 subjects, while in the other 15 the changes were opposite. Peripheral glucose disposal was improved in 11 of the subjects. In the majority of the subjects, substantial increase of serum high-density lipoprotein (HDL) cholesterol and significant decrease of serum Na+ concentration were also seen-the latter possibly due to activation of a Na+/H+ antiporter by the decreased intracellular deuterium level. The results support the possible beneficial role of DDW in disorders of glucose metabolism but leave questions open, requiring further studies.

Deuterium-Depleted Water as Adjuvant Therapeutic Agent for Treatment of Diet-Induced Obesity in Rats.

In this study, we present the potential application of deuterium-depleted water (DDW) for the prevention and adjuvant treatment of obesity in rats. We tested the hypothesis that DDW can alleviate diet-induced obesity (DIO) and its associated metabolic impairments. Rats fed a high-fat diet had an increased body weight index (BWI), glucose concentration, and level of certain proinflammatory cytokines; decreased levels of insulin in the serum; decreased tryptophan and serotonin in the brain, and a decreased concentration of some heavy metals in the liver. Drinking DDW at a concentration of 10 ppm deuterium/protium (D/H) ad libitum for 3 weeks restored the BWI, glucose (serum), tryptophan (brain), and serotonin (brain) levels and concentration of Zn in the liver in the DIO animals to those of the controls. The levels of proinflammatory cytokines (IL-1ß, IL-6, IFNγ) and anti-inflammatory TNFα were decreased in DIO rats, while anti-inflammatory cytokine (IL-4, IL-10) levels remained at the control levels, which is indicative of a pathophysiological syndrome. In contrast, in groups of rats treated with DDW, a significant increase in anti-inflammatory (IL-4, IL-10) and proinflammatory cytokines (IFNγ) was observed. This finding indicates a reduction in systemic inflammation in obese animals treated with DDW. Similarly, the high-fat diet caused an increased level of oxidative stress products, which was accompanied by decreased activity of both superoxide dismutase and catalase, whereas the administration of DDW decreased the level of oxidative stress and enhanced antioxidant enzyme activities.

[Influence of meat semiprepared foods produced with an addition of water having a reduced deuterium content on the indicators of the laboratory animals with the model of alloxan diabetes].

The paper presents the results of the study on the influence of water with a reduced deuterium content and the meat semi-prepared foods produced with its addition on the indicators of the laboratory animals with the model of alloxan diabetes. The effect of low concentrations of deuterium on the body weight dynamics was shown as well as the manifestation of glucosuria and ketonuria, and clinico-biological indicators of the animal's blood. The experiment was carried out during 42 days on male rats of Wistar stock, which were divided into 4 groups - 2 experimental, control (n=10) and intact (n=6), and consisted of three stages: adaptational, the stage of modeling of alloxan diabetes (a single intraperitoneal injection of alloxan monohydrate - 12 mg/100 g body weight) and dietic therapeutic. The animals of the experimental groups consumed water with a reduced deuterium content and standard vivarium diet or the meat minced semi-prepared products produced with its addition and cooked to culinary readiness. The control group consumed tap water and standard vivarium diet. In animals of the 1st group, which consumed the meat product, glucosuria persisted up to the 28th day (the 11th day after administration of alloxan), ketonuria up to the 34th day (the 17th day after modeling). In rats of the 2nd group, which consumed water with the decreased deuterium content, glucose in urea was not detected already on the 7th day after administration of alloxan, ketones on the 17th day after modeling of the disease, respectively. In animals of the control group, glucosuria and ketonuria persisted up to the end of the experiment. As a result of the investigations, the positive effect of water with a reduced deuterium content and the meat food produced with its use was established. It was manifested in a decrease of glucose level in the urea of the animals from the experimental groups compared to the control group on the 5th day of disease modeling and normalization on the 17th day of modeling. This experimentally demonstrated the possibility to use deuterium-depleted water in a meat product composition intended for nutrition of people with an impairment of carbohydrate metabolism for correction of metabolic processes.

Study of the Effects of Deuterium-Depleted Water on the Expression of GLUT4 and Insulin Resistance in the Muscle Cell Line C2C12.

Deuterium-depleted water (DDW) is used in the treatment of many diseases, including cancer and diabetes. To detect the effect of DDW on gene expression and activation of the insulin-responsive transporter GLUT4 as a mechanism for improving the pathology of diabetes, we investigated the GLUT4 expression and glucose uptake at various concentrations of DDW using the myoblast cell line C2C12 differentiated into myotubes. GLUT4 gene expression significantly increased under deuterium depletion, reaching a maximum value at a deuterium concentration of approximately 50 ppm, which was approximately nine times that of natural water with a deuterium concentration of 150 ppm. GLUT4 protein also showed an increase at similar DDW concentrations. The membrane translocation of GLUT4 by insulin stimulation reached a maximum value at a deuterium concentration of approximately 50-75 ppm, which was approximately 2.2 times that in natural water. Accordingly, glucose uptake also increased by up to 2.2 times at a deuterium concentration of approximately 50 ppm. Drug-induced insulin resistance was attenuated, and the glucose uptake was four times higher in the presence of 10 ng/mL TNF-α and three times higher in the presence of 1 µg/mL resistin at a deuterium concentration of approximately 50 ppm relative to natural water. These results suggest that DDW promotes GLUT4 expression and insulin-stimulated activation in muscle cells and reduces insulin resistance, making it an effective treatment for diabetes.

The biological impact of deuterium and therapeutic potential of deuterium-depleted water.

Since its discovery by Harold Urey in 1932, deuterium has attracted increased amounts of attention from the scientific community, with many previous works aimed to uncover its biological effects on living organisms. Existing studies indicate that deuterium, as a relatively rare isotope, is indispensable for maintaining normal cellular function, while its enrichment and depletion can affect living systems at multiple levels, including but not limited to molecules, organelles, cells, organs, and organisms. As an important compound of deuterium, deuterium-depleted water (DDW) possess various special effects, including but not limited to altering cellular metabolism and potentially inhibiting the growth of cancer cells, demonstrating anxiolytic-like behavior, enhancing long-term memory in rats, reducing free radical oxidation, regulating lipid metabolism, harmonizing indices related to diabetes and metabolic syndrome, and alleviating toxic effects caused by cadmium, manganese, and other harmful substances, implying its tremendous potential in anticancer, neuroprotective, antiaging, antioxidant, obesity alleviation, diabetes and metabolic syndrome treatment, anti-inflammatory, and detoxification, thereby drawing extensive attention from researchers. This review comprehensively summarizes the latest progress in deuterium acting on living organisms. We start by providing a snapshot of the distribution of deuterium in nature and the tolerance of various organisms to it. Then, we discussed the impact of deuterium excess and deprivation, in the form of deuterium-enriched water (DEW) and deuterium-depleted water (DDW), on living organisms at different levels. Finally, we focused on the potential of DDW as an adjuvant therapeutic agent for various diseases and disorders.

Deuterium-Depleted Water in Cancer Therapy: A Systematic Review of Clinical and Experimental Trials.

Chemotherapy exhibits numerous side effects in anti-tumour therapy. The clinical experiments indicated that deuterium-depleted water (DDW) monotherapy or in combination with chemotherapy was beneficial in inhibiting cancer development. To further understand the potential mechanism of DDW in cancer therapy, we performed a systematic review. The data from experiments published over the past 15 years were included. PubMed, Cochrane and Web of Science (January 2008 to November 2023) were systemically searched. Fifteen studies qualified for review, including fourteen in vivo and in vitro trials and one interventional trial. The results showed that DDW alone or in combination with chemotherapy effectively inhibited cancer progression in most experiments. The combination treatment enhances the therapeutic effect on cancer compared with chemotherapeutic monotherapy. The inhibitory role of DDW in tumours is through regulating the reactive oxygen species (ROS)-related genes in Kelch-like ECH-associated protein 1 (Keap 1) and Nuclear erythroid 2-related factor 2 (Nrf2) signalling pathways, further controlling ROS production. An abnormal amount of ROS can inhibit the tumour progression. More extensive randomized controlled trials should be conducted to evaluate the accurate effect of DDW in Keap1-Nrf2 signalling pathways.

Nafion: A Flexible Template for Selective Structuring.

The peculiarities of crystal growth on a Nafion polymeric substrate from supersaturated aqueous solutions of initial substances were studied. The solutions were prepared based on deionized natural water and deuterium-depleted water. As was found earlier, in natural water (deuterium content 157 ± 1 ppm) polymer fibers are capable of unwinding towards the bulk of the liquid, while in deuterium-depleted water (deuterium content ≤ 3 ppm) there is no such effect. Since the distance between the unwound fibers falls in a nanometer range (which is close to the size of the unit cell of the crystal lattice), and these fibers are directed normally to the polymeric substrate, the unwinding can affect crystal growth on the polymer substrate. As was obtained in experiments with X-ray diffractometry, the unwound polymer fibers predetermine syngony of crystals, for which the unit cell is either a rectangular parallelepiped (monoclinic system) or an oblique parallelepiped (triclinic system). A quantitative theoretical model that describes the local interaction of the polymer substrate with the crystalline complexes is presented. Within this model, the polymer substrate can be considered as a flexible matrix for growing crystals.

A Preliminary Study Indicating Improvement in the Median Survival Time of Glioblastoma Multiforme Patients by the Application of Deuterium Depletion in Combination with Conventional Therapy.

Glioblastoma multiforme (GBM) and malignant gliomas are the most common primary malignant brain tumors. Temozolomide (TMZ) chemotherapy plus radiation therapy (RT), admi-mistered after debulking surgery, increased the median survival time (MST) from 12.1 months with RT alone merely to 14.6 months, respectively. In this study, the actions of deuterium-depleted water (DDW) on the survival of GBM patients who also received conventional therapies was investigated. Without changing the conventional treatment, the daily fluid intake of the patients was wholly replaced with DDW in 1.5-2 L per day volume to reduce the D concentration in their bodies. The primary endpoint was the MST. The 55 patients involved in this study, who received conventional treatment and consumed DDW, showed a longer MST (30 months) compared to the historical control (12.1-14.6 months). There was a massive difference between the two genders in the calculated MST values; it was 25 months in the male subgroup (n = 33) and 42 months in the female subgroup (n = 22), respectively. The MST was 27 months without TMZ treatment (38 patients) and 42 months in the TMZ-treated group (17 patients), respectively. For the selected 31 patients, who consumed DDW in the correct way in addition to their conventional treatments, their MST was calculated as 30 months. Within this group, the 20 subjects who had relapsed before DDW treatment had 30 months of MST, but in those 10 subjects who were in remission when DDW treatment started, their MST was 47 months. In the subgroup of patients who began their DDW treatment parallel with radiotherapy, their MST was again 47 months, and it was 25 months when their DDW treatment was started at 8 weeks or later after the completion of radiotherapy. Altogether, these survival times were substantially prolonged compared to the prospective clinical data of patients with primary GBM. Consequently, if conventional therapies are supplemented with D depletion, better survival can be achieved in the advanced stage of GBM than with the known targeted or combination therapies. Application of DDW is recommended in all stages of the disease before surgery and in parallel with radiotherapy, and repeated DDW courses are advised when remission has been achieved.